Improvement of the Solubility and Evaluation of the Physical Properties of an Inclusion Complex Formed by a New Ferulic Acid Derivative and ?-Cyclodextrin.

ABSTRACT: Ferulic acid derivative 012 (FAD012) is a ferulic acid (FA) derivative. The current study prepared a solid dispersion of FAD012 and ?-cyclodextrin (?CD) and ground it using a three-dimensional ball mill (3DGM) to prepare an inclusion complex. This study also assessed the physicochemical properties such as solubility of that complex. A Job's plot indicated that FAD012 and ?CD formed an inclusion complex at a molar ratio of 1:1. Phase solubility diagrams revealed that FAD012 produced a BS diagram. According to PXRD, FAD012 produced a diffraction peak at 2? = 7.0° and ?CD produced a diffraction peak at 2? = 9.1°. Those two peaks were not produced by the 3DGM, but new peaks (2? = 7.3 and 16.5°) were evident. DSC patterns revealed an endothermic peak due to the melting of FAD012 at 190 °C, but no endothermic peaks were evident with the 3DGM. NIR spectra of the 3DGM indicated that the methyl group of FAD012 produced a higher peak and that the OH groups of ?CD produced a higher peak. 1H-1H ROESY NMR spectra (D2O) revealed cross peaks for protons of the methyl group of FAD012 and a proton (H-3) in the cavity of ?CD, so FAD012 presumably interacts with the wide opening of the ?CD torus. A solubility test (25 °C) indicated that solubility improved about 5-fold for the 3DGM in comparison to the solubility of FAD012 alone (about 140 ?g/mL). Based on these findings, an FAD012/?CD complex was formed by cogrinding, and its solubility improved. These observations are expected to expand the usefulness of cogrinding of FAD012 with ?CD using a 3D ball mill.

SUBMITTER: Ikeda N 

PROVIDER: S-EPMC7271043 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature